Bladder cancer is the fourth most common neoplasm worldwide in males with notoriously high recurrence and chemo-therapy refractoriness. Transitional cell carcinoma (TCC) accounts for more than 90% and squamous cell carcinoma for about 6% to 8% of bladder tumors. Bladder cancer is often heterogeneous. That is, there are more than one sub-types of bladder cancer cells in a bladder cancer patient.
In chemotherapy, the response rates are fairly low, usually between 5%-55%. The low success rate is at least in part because of cancer heterogeneity. A therapy that is suitable for one sub-type of cancer cells may not be efficacious for another. Combination chemotherapies that simultaneously target several mechanisms in cancer cells, in particular those involved in cancer cell survival, are expected to have better therapeutic index than mono-drug regimens. This has shown success for fairly homogenous cancers but it is not clear whether combination therapies have similar advantage for heterogeneous cancers like bladder cancer.
Searching for a potential optimal combination from a large pool of drugs is a prohibitive task, and more so for a cancer such as bladder cancer with high heterogeneity. Therefore, there is a need for improved methods for efficiently identifying potentially useful drug combinations for treating bladder cancer as well as the resulting combinations.